This protocol will permit the evaluation and treatment of subjects with hereditary and acquired hemolytic diseases, to facilitate understanding of the pathogenesis and natural history of vaso-occlusive painful crisis and pulmonary complications of sickle cell disease and related cardiopulmonary complications of other hereditary, acquired and iatrogenic hemolytic disorders. We will also investigate the polymorphisms that have been linked to pulmonary hypertension to determine whether genetic polymorphisms in candidate genes contribute to the development of pulmonary hypertension or response to treatment. Patients will be evaluated with a medical history and physical examination and routine laboratory studies will be obtained as needed to assess diagnosis, disease activity, and disease complications and to monitor for treatment-related responses and toxicities. Blood can be obtained, with subjects consent, for research studies evaluating gene/protein expression and to evaluate the role of vasodilators, vasoconstrictors, inflammatory and redox stress mediators in this population. Patients identified with pulmonary hypertension will have the option to undergo invasive hemodynamic evaluation and treatment with FDA approved drugs, according to current standards of medical practice, with signed informed consent for all offered procedures. Patients eligible for other research protocols will be offered an opportunity to participate in these studies by signed informed consent. Apart from such protocols, any medical care recommended or provided to the patient will be consistent with routine standards of practice and will be provided in consultation with the patients referring physician. In addition to the clinically indicated tests we revised the study to include peripheral arterial tonometry, an FDA approved non-invasive technology that captures a beat-to-beat plethysmographic recording of the finder arterial pulse wave activity with pneumatic probes. We also included passive infrared photography for assessment of blood flow distribution and vasomotion and are performing candidate gene analysis on the blood obtained from the subjects enrolled in this study to investigate the potential determinants or genetic risk factors for the development of pulmonary hypertension. We have successfully enrolled a total of 246 subjects to date. 229 of these subjects were sickle cell patients and 17 subjects were diagnosed with other hemolytic disorders. We continue to gather clinical data and experience related to the care of patients with sickle cell disease and other hemolytic disorders.